The purposeof the Hematologic Malignancy Program is to develop laboratory-based treatment programs that will lead to improvements in long-term, disease-free survival following allogeneic or autologous bone marrow transplantation and widen the applicability of the therapy. This progress is dependent upon the development of novel therapeutic programs to decrease relapse and to prevent complications of the therapy. During the previous funding periods, we completed a series of Phase I, II and III trials in both allogeneic and autologous transplantation which have led to improvements in the outcome for patients with hematologic malignancy. These include allogeneic transplant trials in leukemia; graft-versus-host disease and CMV infection; and autologous transplant in Hodgkin's disease, multiple myeloma, AML and lymphoma. During this time, progress in our understanding the immunology of CMV has facilitated the development of peptide-based immunization trials to control CMV infection after transplantation. The first trials utilizing retroviral-mediated gene transfer of ribozymes that convey resistance to HIV were performed for patients undergoing autologous BMTfor HIV lymphoma. In addition, programs in hematopoiesis and tumor immunology focused on leukemia and lymphoma were also developed. Importantly, the construction of the Center for Biomedicine and Genetics was planned and completed. This biologic production facility enables us to perform novel clinical studies utilizing radioimmunotherapy for treatment of leukemia and lymphoma, genetic modification of T cells targeted to leukemia and lymphoma andgene therapy trials in HIV lymphomautilizing AAV and lentivirus. The work accomplished in the previous funding period, the clinical expansion of the program and the introduction of new investigators will allow us to achieve our goals for the next funding cycle which include: 1. To improve the longterm, disease-free survival of patients with hematologic malignancy undergoing allogeneic or autologous hematopoietic stem cell transplantation. 2. To use novel interventions for genetic manipulation of hematopoietic cells, radioimmunotherapy,antigen specific T-cell immunotherapy and peptide immunizations to accomplish these goals. 3. To develop Phase I and Phase II clinical trials that can be tested in larger patient populations or in comparative trials in the cooperative group setting. The 48 members of the Hematologic Malignancies program have published 403 articles, book chapters, etc., since the last competitive grant review. Of these, 209 are intraprogrammatic and 173 are interprogrammatic publications.